Commission K : ELECTROMAGNETICS IN BIOLOGY AND MEDICINE (Nov. '95 - Oct. '98)

Edited by Shoogo Ueno and Masao Taki

K1. Biological Effects of Electromagnetic Fields

K1.1. Electric Fields

A series of studies have been made in Hokkaido University and Hokkaido Institute of Technology. The perception threshold of an ELF electric field is one of the important factors to evaluate biological effects and to determine safety standards. The perception threshold varies in different conditions and in different individuals. The characteristics of the variance were investigated. The change in the relative humidity is one of the predominant factors to cause the variance. The threshold is also dependent on the physical conditions (length and density) of the hair and on the psychological conditions of the subject. The gender difference is ascribed to the difference in the physical condition of the hair. [Odagiri, 1996; Shimizu, 1998]



K1.2. Static Magnetic Fields

Biological effects of static magnetic fields have been poorly understood. Recognition of the role of paramagnetic, diamagnetic and ferrimagnetic materials in the body may help in unraveling the underlying mechanisms.

I. Magnetic Orientation of Red Blood Cell

Higashi et al. studied static magnetic field orientation of erythrocytes which hardened by glutaraldehyde [Higashi, 1996]. Takeuchi et al. compared it with orientation of normal erythrocytes studied previously [Takeuchi, 1995]. The normal erythrocytes are oriented with their disk plane parallel to the magnetic field direction by diamagnetic anisotropy of their membrane components. But the hardened erythrocytes are perpendicularly orientated by paramagnetic anisotropy of methemoglobin which combines with the cell membrane. These research were reviewed [Higashi , 1995]. Higashi et al. showed that blood platelets are always orientated with their disk plane parallel to the magnetic field [Higashi, 1997]. Magnetic orientations of red blood cells with plasma proteins were also investigated by measuring electrical conductivity [Suda, 1996].

II. Genetic Effects of Static Magnetic Field

The genetic effects of magnetic fields on somatic reversion and somatic recombination in Drosophila melanogaster have been reported by Yoshikawa et al.[1995]. They examined the somatic reversion of the white locus and the somatic recombination of mwh and fly genes in Drosophila melanogaster after they were exposed to a static magnetic field at 8 T. The static magnetic fields with 8 T were effective in producing the eye spots caused by intragenic mutation and the wing hair spots resulting from somatic recombination. In the exposure groups, eye spots occurred 1.7 times more frequently than in the control groups, and wing hair spots 1.4 times more.

III. Polymerization and Dissolution of Fibrin under Homogeneous Magnetic Fields

Iwasaka et al.[1998a] investigated whether or not a mutually compensating state of coagulation and fibrinolysis is changed by homogeneous magnetic fields. Fibrin polymerization over time, and the subsequent dissolution of the fibrin fiber network, were observed by measuring the optical absorbance of the mixture at 350 nm. A magnetic field of 14 T increased the rate of the polymerization process by 55% - 70% compared to the control group. On the other hand, the rate of the fibrinolytic process under a magnetic field at 14 T, increased by 27% - 140% compared to the control. The results indicate that the magnetic orientation of fibrin fibers accelerated both the polymerization and the dissolution of fibrin fibers.

IV. Bioluminescence under Static Magnetic Fields

The effect of magnetic fields on the emission of light by a living system was studied by Iwasaka and Ueno [1998c,d]. The firefly Hotaria parvula and Luciola cruciata were used as the bioluminescence systems. They measured the time course of emissions at 550 nm in a transient emission state. The rate in the light intensity under an 14 T magnetic field increased compared to the control. There is a possibility that the change in the emission intensities under a magnetic field is related to a change in the biochemical systems of the firefly, such as the enzymatic process of luciferase and the excited singlet state with subsequent light emission.

V. Properties of Water under Magnetic Fields

Ueno et al. studied the properties of diamagnetic water in static magnetic fields. The phenomenon that the surface of the water was pushed back by magnetic fields of higher gradients was observed [Iwasaka, 1998a]. They investigated the effects of strong magnetic fields of up to 14 T on the near-infrared spectrum of water molecules. We used a near-infrared spectrophotometer which has an external optical cell box in a 14 T superconducting magnet. Iwasaka et al. measured the near-infrared spectrum of water in the range of 900 nm-2000 nm by changing the optical path lengths from 0.1 mm to 100 mm. The peak wavelengths in the near-infrared spectrum in the range of 900 nm to 2000 nm of water, increased in length by 1-3 nm under a 14 T magnetic field. There is a possibility that the 14 T magnetic field affects on the formation of hydrogen bonds of water molecules.

VI. In Vivo

In vivo studies on static magnetic fields (SMF) were performed in the experimental animal. One group mainly evaluated relatively weak SMF (1 mT), other groups evaluated strong SMF (5-8 T).

A series of in vivo studies on microcirculatory system in animals have been made in Department of Physiological Hygiene, National Institute of Public Health, Ministry of Health and Welfare. Effects of local and whole body exposures of SMF on cutaneous microcirculation within a rabbit ear chamber under conscious conditions and skeletal muscle microcirculation under anesthetized conditions in mice were studied intravital-microscopically. Concurrent with intravital-microscopic study, blood pressure and heart rate were also monitored. Rabbits with ear chamber were subjected to microphotoelectric plethysmography. Following the acute exposures (< 1 minute) of SMF, the spontaneous and continuous rhythmic fluctuation of microvascular blood flow due to vasomotion was modified. There was no dose-response relationship between the extent of vasomotion changes and power levels of SMF (1, 5, 10, 100 mT). One mT of SMF for 10 minutes modulated the vascular tone biphasically [Ohkubo,1997a,b]. Subacute exposure of SMF (180 mT) for several weeks induced enhancement of vasomotion and dilatation of arterioles[Xu,1998a]. Under pharmacologically induced low vascular tone acute exposure (10 minutes) of SMF evoked vasoconstriction [Ohkub,1997c,1998, Okano, 1998,1999]. In contrast, under pharmacologically induced high vascular tone, it did vasodilatation [Okano et al. 1998, 1999]. By 10 minutes' whole body exposure to SMF (1 mT), the capillary blood flow velocity of quadriceps femoraris was accelerated and carotid blood pressure was elevated from its low level due to anesthesia. Concurrently the heart rate decreased [Xu, 1998b]. These changes in blood pressure and heart rate including microcirculatory parameter were also recognized in rabbits under conscious conditions at higher doses of SMF (>200mT) which was applied to the skin surface ares of the carotid sinus [Gmitrov,1997,1998]. The results mentioned above indicate that relatively weak SMF can modulate beneficially both micro- and macrocirculation under untoward conditions. These results suggest that the SMF in a certain intensity can modulate vascular tone beneficially due to modification of vasomotion, biphasically.

Tsuji et al.[1996] exposed mice to a 5 T static magnetic field for 48 h and found decrease of food and water intake, weight-loss, and increased BUN levels. These results were considered due to body fluid loss resulting from anxiety of moving in the strong static magnetic field. Watanabe, Y. et al.[1997] measured lipid peroxidation in the liver, kidney, heart etc. of mice exposed to a 4.7 T field, and also evaluated the effects of SMF on the hepatotoxicity induced by treatment with carbon tetrachloride. The results indicated that the exposure to a strong SMF induces lipid peroxidation in mouse liver and enhances the hepatotoxicity of CC14. Mutagenicity of static magnetic fields was studied by means of the Drosophila SMART (Somatic Mutation and Recombination Test) system. Koana et al.[1995] reported that exposure to a 600mT SMF caused damage to cellular DNA of mutagen sensitive mutants. Koana et al.[1997] found that a 5T field caused mitoic recombination. As the effect was suppressed by supplement of a radical scavenger, involvement of free radicals in the mutational process was suspected.

The acute effects of strong SMF(up to 8 T) exposure on microcirculation by use of dorsal skin chamber was studied intravital-microscopically in rats. After exposure of SMF for 20 minutes, microcirculatory blood flow showed an initial increase for about 5 min followed by a gradual decrease and a return to the control value. It is hypothesized that these changes represent rebound hyperemia following reduced blood flow during exposure [Ichioka 1998].

Threshold effects of static magnetic fields on the current distributions induced around the ascending and descending aortas and their related blood flow changes are evaluated theoretically by use of a finite element analysis [Kinouchi, 1996a].

VII. In Vitro

A new system for bacterial cultivation which operates under a high magnetic field in the range of 0.5 to 7 Tesla was developed [Okuda, 1995]. The several repair deficient mutants of E. coli were cultivated in homogeneous 7 T field and 5-6 T inhomogeneous field and no adverse effects of magnetic field were observed [Shoda, 1996]. Enhancement of survival degree and the inhibition of spore formation of Bacillus subtilis were observed under 7 Tesla homogeneous and 5.2-6.1 Tesla inhomogeneous magnetic field [K.Nakamura, 1997]. In the stationary phase, degree of survivability of Escherichia coli was higher under a high magnetic field than that of a control [Tsuchiya, 1996]. The effect of high magnetic field on bacterial cells was reviewed mainly based on the author's research data [Shoda, 1997].



K1.3. ELF Fields

The effects of switched 1.6 T fields with a period of 3 seconds on cell ion transportations in vitro have been studied in series at University of Tokushima. The fields suppressed the increase of quinine-sensitive K+ influx in high K+ concentration medium [Park, 1996] and also suppressed the increase of intracellular Ca2+ induced bradykinin in Ca2+-free medium [Ikehara, 1998 and Park et al., 1998]. From theoretical viewpoints, an ion cyclotron resonance and its threshold effects [Kinouchi et al., 1996b], and related electromagnetic mechanisms [Kinouchi, 1997] have been evaluated. The series of these studies have been reviewed [Miyamoto, 1998].

Within a past few years, a series of studies have been made in Hokkaido University and The Central Research Institute of Electric Power Industry. Their research focused on the effects of 50Hz magnetic fields on melatonin. The overview of research was presented [Kato, 1996, 1997a,b]. They pointed out that the effects depend on not only magnetic fields strength, but also on the directions of magnetic fields (linear, circular). This is important point when the dosimetry should be taken in consideration of magnetic field effects. Three studies was finished [Yasui,1997; Kikuchi,1998; Negishi,1998]. Yasui et al.[1997] investigated the possible effects of 50Hz, 5mT, linearly polarised magnetic field on the carcinogenicity in rat. This study showed no evidence that magnetic field exposure enhanced the development of leukemia. This was considered as a key study because of the high field exposure and the good engineering. Kikuchi et al [1998] investigated the effects of 50Hz, 5mT, linearly polarized magnetic fields on the mutations of Drosophila melanogaster for 40 generations. As a result, there was no difference among the groups in either enhancing nor suppressive effects on incidence of weakly deleterious mutations. In addition, Negishi et al [1998] investigated the possible effects of 50Hz, 0, 7, 70, 350 micro T circularly polarized magnetic fields on maternal reproductive function in golden hamsters. Based on exposure experiments, it was concluded that magnetic field did not affect reproduction and teratogenesis of the fetuses in golden hamsters.

Miyakoshi et al.[1996a] found that exposure to ELF magnetic field of 400 mT and 50 Hz induced mutations in HPRT gene of human MeWo cells. The mutations induced by the high-density ELF magnetic field increased during the DNA-synthesis phase in synchronously growing MeWo cells [Miyakoshi, 1997] and were suppressed by expression of the introduced wild-type p53 gene during the magnetic exposure in human osteosarcoma Saos-2 cells [Miyakoshi, 1998b]. They also found that exposure to the ELF magnetic field at 400 mT enhanced b-galactosidase activity stimulated by treatment with forskolin in rat PC12-VG cells [Miyakoshi, 1995 and Ohtsu, 1995] and expression of neuron derived orphan receptor (NOR-1) gene in Chinese hamster ovary cells [Miyakoshi, 1998a]. No significant difference in the c-myc expression of CHO cells was observed with 5 mT ELF magnetic field exposure [Miyakoshi, 1996b].



K1.4 RF and Microwaves

Studies on the promotion of the rat liver carcinogenesis were made by researchers of Nagoya City University, Tokyo Metropolitan University, and Communications Research Laboratory, Ministry of Posts and Telecommunications. Time division multiple access (TDMA) signals for the Personal Digital Cellular (PDC) Japanese cellular telephone standard system were directed to rats through a quarter-wavelength monopole antenna at 929.2 MHz [Imaida, 1998a] and at 1.439 GHz [Imaida, 1998b]. In these experiments, local SARs in the liver were about 2 W/kg while the whole-body-averaged SARs were less than 0.8 W/kg. These experiments were therefore under non-thermal condition. No significant effect on rat liver carcinogenesis was found.

The effects of pulsed high-frequency electromagnetic field on the healing of open wound were studied in the rabbit ear[Ide, 1998].



K2. Tissue Properties and Materials

The phantom is one of the most important targets of the dosimetric studies. Japanese researchers developed various solid phantoms. A dry phantom material was composed of high-permittivity ceramic powder, graphite powder, and bonding resin [Tamura, 1997]. This "dry" phantom has very good stability. A wet and solid phantom was developed by adding agar to the recipe of the conventional jelly phantom [Y.Okano, 1998]. The composition of this phantom material was also optimized to simulate the electrical properties of brain tissue over UHF region. Furthermore, a soft and dry phantom material using silicone rubber with carbon fiber was developed [Nikawa, 1996].

Ito [1998a, 1998b], Furuya [1995] et al. developed a biological tissue-equivalent phantom for microwaves. The phantom consists from agar, deionized water, TX-151, polyethylene powder, sodium chloride and the preservative. The phantom realizes nearly the same electric properties as those of high-water-content tissues, within the range of operating frequencies from 200 MHz to 2.5 GHz in single recipe. The preparation is simple and the phantom can be preserved at room temperature for several months. As for the application of the phantom, Okano and Ito [1998] investigated the characteristics of the small slot antenna for wrist-watch-type pager near the cylindrical human body phantom model. It was revealed that the phantom model was sufficient for measuring such characteristics as the far-field radiation pattern of the antenna. The phantom is recommended as a tissue-equivalent phantom for microwave heating by the Japanese Society of Hyperthermic Oncology [Mizushina et al. 1998].

FD-TD analysis and exposure test have been carried out to show the validity of local SAR measurement using the polyacrylamide phantom containing non-ionic surface active agent [Miyakawa, 1996]. Polyacrylamide phantom containing non-ionic surface active agent has been developed to visualize the three dimensional distribution of local SAR inside the human body [Miyakawa,1998].



K3. Field Measurement and Exposure Assessment

K3.1. ELF Fields

In the Central Research Institute of Electric Power Industry (CRIEPI), some bioengineering and engineering researches have been conducted. Methods to calculate induced current inside the body, using the charge simulation method or the surface charge method, were developed and adopted to a cylindrical model, a human-head model, and a whole human-body model consisting of organs simulated using spheroids and cylinders [Yamazaki, 1996a,b,c, 1998a].

A multi-functional magnetic field meter capable of measuring field ellipses was developed [Yamazaki, 1996d]. Two mitigation methods for power line magnetic fields were investigated using model experiments and numerical analyses. One was a method for underground power line cables using pipe-type shielding materials [Yamazaki, 1997, 1998a,b,c], and the other was for overhead power lines using an auxiliary loop conductor [Yamazaki, 1998d]. Conditions for effective mitigation were clarified for both mitigation methods.

Induced current density is numerically estimated during exposure to ELF magnetic field to cause magnetophosphenes using realistic human head model with impedance method [Wake, 1998]. The estimated current density in retina is consistent with previously estimated values with simplified models. Induced current density is calculated in a analytical head model during use of an electric shaver [H.Nakamura, 1996].



K3.2. RF and Microwaves

The SAR distribution in a human body exposed to near-field of a small radiation source in the whole-body-resonance frequency region, i.e., 30 MHz - 300 MHz, was calculated and the relation to the exposure guidelines in those frequency region were discussed [S.Watanabe, 1996a].

The SAR dosimetry for a human head exposed to near-field from a cellular telephone has become one of the most interesting subjects. The numerical dosimetry using a realistic human head model exposed to the near-field from a cellular telephone were investigated by using numerical and experimental approaches [S.Watanabe, 1996b]. The dependence of the local SAR on the definition of the averaging local region was also investigated [Taki, 1996]. Furthermore, the characteristics of the antenna of a cellular telephone positioned close to a human head was investigated [S.Watanabe, 1996b].

A series of studies on the analytical dosimetry at frequencies for mobile phones have been conducted in Nagoya Institute of Technology. Effects of the electrical properties of skin tissue on the specific absorption rate (SAR) in a human head have been examined numerically, with the idea that the skin could play an electromagnetic shielding role [Fujiwara, 1997]. The tissue structure dependence on the SAR in a human head has also been investigated, which suggests the usefulness of a realistic shaped homogeneous model [Nomura and Fujiwara, 1998]. Based on the consideration that a localized SAR exposure limit should be determined from the resultant temperature-rises, the temperature-rises in a human head have been computed for both plane-wave exposure and mobile phones by using the FDTD method [Fujiwara,1998; Takai and Fujiwara, 1998; Wang and Fujiwara, 1998]. Moreover, a new method has been proposed for reducing the localized SAR in a human head by ferrite sheet attachment to a mobile phone [Wang and Fujiwara, 1997].

The protection of the human body against strong RF exposure has been studied by several research groups. The decrement of the SAR in a 2-dimensional human model by means of shielding material was calculated with the method of moment [Hashimoto, 1996]. Theoretical analysis was also applied to the estimation of the reduction of SAR in a 2-dimensional human body by lossy dielectric shield [T.Nakamura, 1996]. Furthermore, the directional antennas for portable telephones to contribute the reduction of power absorption into a head resulting in the power saving and increase of a battery life time were studied [Noguchi, 1996].

The improvement of the FDTD model for the antenna feeding model was proposed [S.Watanabe, 1998]. This new model can provide accurate value of the antenna input impedance regardless of the dimension of FDTD cells.



K4. Magnetic Stimulation

A method of localized magnetic stimulation of the brain has been developed by Ueno et al. in 1988. By concentrating induced eddy currents on a target with a pair of opposing pulsed magnetic fields produced by a figure-eight coil, it was able to stimulate the human cortex within a 5 mm resolution. Hyodo et al. [1996] developed a nerve excitation model for localized magnetic stimulation of finite neuronal structure.

Magnetic stimulation of heart was studied by Suzuki et al. [1997]. Magnetic defibrillation is developed as a noninvasive form of medical treatment.

Cardiac muscle can be stimulated by strong pulsed magnetic fields. As a consequence, magnetic defibrillation (MDF) promises to be a non-invasive method for regulating ventricular rhythm. It is the most serious problem how strong magnetic fields are applied to bodies. Kubota et al. [1995] developed high-performance stimulating coils for MDF. Moreover, Wada et al. [1996] and Suzaki et al. [1997] experimentally and theoretically studied stimulus waveforms which are effective to MDF.



K5. Hyperthermia

The number of medical applications of microwaves is increasing, such as hyperthermia, cardiac catheter ablation, MCT (Microwave Coagulation Therapy) and so forth [Ito, 1996a,b, 1997]. Ito et al. investigated on the coaxial-slot antenna for interstitial microwave hyperthermia by both of phantom experiment and computer simulation [Ito, 1997]. Heating characteristics of the array applicator composed of the antenna were examined in the multi-layered media (skin-fat-muscle) by using the FDTD (Finite Difference Time Domain) method [Saito,1998a,b,c]. The effects of arrangement of the slots, catheter thickness and operating frequencies (430 MHz and 915 MHz) on the heating characteristics of the applicator were investigated by using Method of Moments [Hamada,1995, 1996, Saito,1997]. Moreover, Hamada [1998] and Dean [1998] et al. studied the control of heating characteristics of the array applicator by incoherent and coherent feedings. As for the evaluation of the heating characteristics of the antenna, Furuya et al. [1996] proposed an evaluation index about the relations between the SAR pattern and temperature distribution inside the tissue by solving bioheat transfer equation.

The coaxial-slot antenna was also applied to another minimally invasive thermal therapy. Saito et al. [1998b,c] applied the antenna to cardiac catheter ablation for ventricular arrhythmia treatment. SAR distribution generated by the antenna inside heart chamber was calculated by using FDTD analysis, and the calculated results showed the ability of localized heating inside the ventricle.



K6. Medical Diagnosis

K6.1. Magnetoencephalography

Iramina et al. [1998] have developed a multi-channel high-resolution SQUID magnetometer for measuring biomagnetic fields produced by small animals. They measured the magnetocardiogram produced by a rat. Topographies of P-wave, QRS-wave and T-wave of rat MCG were obtained. They also measured the magnetoretinogram, visually evoked magnetic fields and auditory evoked magnetic fields of the rat. The signals of magnetoretinogram appeared at 60 msec latency and the field intensities were about 0.6 pT. It was not possible to obtain the clear visually evoked fields, because those signals were hidden behind the magnetoretinogram. It was possible to obtain auditory evoked magnetic fields of the rat. Iwaki and Ueno [1998] developed weighted minimum-norm source estimation of magnetoencephalography utilizing the temporal information of the measured data.



K6.2. Impedance MRI

Ueno et al. proposed a new and noninvasive method for imaging electrical properties such as conductivity and impedance based on MRI techniques [Ueno, 1998; Mihara, 1998]. The basic idea is to use the shielding effects of induced eddy currents in the body on spin precession. Two types of methods are introduced; (i) a large flip angle method, and (ii) a third coil method. The large flip angle method enhances the shielding effects of conducting tissues at the given Larmor frequency. The third coil method detects the shielding effects of conducting tissues at an arbitrary frequency. Both phantom and animal experiments have been carried out to verify this concept using a MRI system of 7.05 T with a bore size of 183 mm in diameter.



K6.3. Microwave CT

Non-invasive thermometry system using microwaves, ultrasound and so on have been discussed their potential abilities as the thermometry system for a human body [Miyakawa, 1995]. Fast data acquisition has been attempted by introducing the array antenna system and its electronic scan into the chirp radar-type microwave computed tomography [Miyakawa and Hayashi, 1997].

A horn-antenna type applicator is designed to take the highest directivity in the water bolus for medical imaging of microwave transmission CT at 3 GHz [Yamaura, 1995]. Some technical problems realizing the non-invasive temperature measurement using microwave CT are stated in combination with the electrical properties of biological materials [Yamaura, 1996].



K6.4. Radiometry

Recent temperature retrieval methods are reviewed; singular system analysis, bio-heat transfer solution matched with radiometric data, and model-fitting combined with Monte Carlo technique [Mizushina, 1995]. Electromagnetic fields generated by a rectangular waveguide in a flossy dielectric medium is analyzed by modal analysis, and is compared with the results by FD-TD [Mizoshiri, 1995]. Basic principles for non-invasive monitoring by microwave radiometry are reviewed, and recent results of the model fitting method are presented [Mizushina, 1996].

The dosimetric study for the microwave radiometry has been reported [Abe, 1995]. In this study, the near fields of rectangular waveguides in contact with biological bodies were calculated with FDTD method in order to obtain the radiometric weighting function.



K6.5. Telemetry technique

A telemetry technique to measure the human EEG in a strong ELF electric field was developed. It could suppress the effect of the electric interference successfully. In the preliminary study, the change in the amplitude of the EEG was observed. It suggested the change in the vigilance level of the subject. [Yamashita,1998]



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